Research Summary

Elucidating the role of lipids in ion channel function

Ion channels are membrane proteins that perform the vital task of acting as conduits for the passage of ions through otherwise impermeable hydrophobic cellular membranes. Upon application of specific stimuli, ion channels undergo a series of conformational changes leading to the opening or closing of their pores. This process, often referred to as “ion channel gating”, has been the focus of extensive research utilizing electrophysiological techniques. Although extremely insightful, these studies have largely overlooked a fundamental aspect of ion channel function—the roles of surrounding membrane lipids in ion channel gating. The critical importance of lipids in membrane protein function has recently been revealed by crystal structures of membrane proteins showing lipids specifically bound to well-defined lipid-binding sites, and also by functional studies demonstrating modulation of membrane protein activity upon lipid depletion. Furthermore, the recent discovery that several drugs modulate their target ion channels by binding to and modulating the protein–lipid interface, confirms the importance of these interactions. Clearly, elucidating how lipids interact with and influence ion channel gating is critical for understanding ion channel function and could also have a tremendous impact on drug development. Such studies are, however, severely hampered by the paucity of methods to manipulate lipids in cells. My laboratory is developing methods for manipulating the chemical properties of lipids in cells and is utilizing those methods to elucidate the roles of lipids in ion channel function by employing electrophysiological approaches.

Figure Legend: Ion channel function is profoundly modulated by surrounding membrane lipids. The ion channel of interest is shown in green and the adjacent lipids in red. Lipids in the membrane that are not adjacent to the ion channel are depicted in cyan. A family of current traces on the right depicts the electrophysiological characterization of the ion channel.